1.The Effect of GTP Cyclohydrolase I on the Activity and Expression of Tyrosine Hydroxylase and Cell Growth.
Young Jae LEE ; In Sook HAN ; Sang Doe YI
Journal of the Korean Neurological Association 1999;17(1):122-130
BACKGROUND: Parkinson's Disease (PD) is a progressive neurodegenerative disorder characterized by resting tremor, rigidity, and bradykinesia. L-3,4-dihydroxyphenylalanine (L-dopa) has been used for over last 3 decades to treat this disorder, however, its usage is limited due to the reducing effectiveness on time and severe side effects. The best strategy for treating this disorder without serious side effects would be to keep a constant level of dopamine in the brain. This could be achieved by gene or cell therapy using gene(S) involved in dopamine biosynthesis or cells from other individual. For Parkinson's gene therapy, however, there still are controversies on which gene In what combination will yield the best result. In this report, we propose a biochemical background for using GTP cyc]ohydrolase I (GTPCH I) in addition to TH for higher and/or more stable expression of TH. METHODS: TH and GTPCH I cDNA were subcloned into retroviral vectos and resulting recombinant retrovirus packaged in BOSC 23 cells were used to infect NIH-3T3. Confirming successful infections by westers blot analysls, the new cell lines were used to examine steady state TH expression level and TH activity. Furthermore, the effect of ectopic expression of BH4 to the proliferation of these cells were studied. RESULTS: NIH-3T3 cells expressing both TH and GTPCH I showed approximately 10 fold higher expression of TH protein than the cells expressing TH alone. The activity of KNTH2GC6 was approximately 4-6 fold higher than that of striatal tissue and 60 fold higher than KNTH2. Furthermore, growth rate of KNTH2GC6 was strikingly reduced by inhibiting the biosynthesis of BH4. CONCLUSIONS: We showed that the use of GTPCH I in addition to TH not only increased the stability and/or expression of TH protein but also the activity of the enzyme. These improved characteristics of TH protein are very likely due to the expression of BH4 and should be very seriously considered for Parkinson's gene therapy.
Brain
;
Cell Line
;
Cell- and Tissue-Based Therapy
;
DNA, Complementary
;
Dopamine
;
Genetic Therapy
;
GTP Cyclohydrolase*
;
Guanosine Triphosphate*
;
Hypokinesia
;
Levodopa
;
Neurodegenerative Diseases
;
NIH 3T3 Cells
;
Parkinson Disease
;
Retroviridae
;
Tremor
;
Tyrosine 3-Monooxygenase*
;
Tyrosine*
;
Zidovudine
2.Clinical Features and Long-Term Follow-up Results in Fifty Four Patients with Aortic Dissection.
Jang Ho BAE ; Kee Sik KIM ; Chang Yeob HAN ; Yi Chul SYNN ; So Young PARK ; Dae Woo HYUN ; Yoon Nyun KIM ; Kwon Bae KIM
Journal of the Korean Society of Echocardiography 1997;5(2):164-171
BACKGROUND: Aortic dissection is an uncommon disease but early mortality is as high as 1 percent per hour if untreated. However, major advances in the prompt noninvasive diagnosis and in the medical and surgical treatment of aortic dissection now improve the survival rate to an 75~82% of 5-year survival rate. In order to determine clinical features and long-term follow up results of patients with aortic dissection in Korea, we present a retrospective review of 54 patients with aortic dissection at our institute. METHODS: We review the medical records, echocardiograms and computed tomogram(CT) or magnetic resonance imaging(MRI) of 54 patients(mean age: 59+/-12 years, male: 27) who had aortic dissection between September 1991 and July 1997. Patients were classified according to DeBakey type. Clinical features were evaluated in relation to type. Long-term survival rate using Kaplan-Meier method were also evaluated in relation to type, sex and presence of undertaking operation. RESULTS: Of the 54 patients with aortic dissection, twenty two(41%) were classified to type I, eight(15%) to type II and twenty four(44%) to type III. Age(type I: 60 yrs, type II: 60 yrs, type III: 57 yrs), sex(male in type I: 10(45%)type II: 4(50% ), type III: 13(54%)) and pulse rate(type I: 84, type II: 75, type III: 78) according to the type of aortic dissection show no signifiant difference. In regarding to predisposing factors, hypertension was found in 40(74%) overall, Marfan syndrome 1(2%), bicuspid aortic valve 4(7%), and iatrogenic vascular injury 3(6%). Four-year survival rate was 48% in all patients who were followed for 28+/-26 months(1-168 months), 61% in type I, 44% in type II and 44% in the III. But, there are no statistically significant difference in 4-year survival rate according to type and sex or presence of undertaking operation(data not shown). There are many kinds of cause of death; multi-organ failure, renal failure, congestive heart failure, sepsis, ruptured aortic dissection, gastrointestinal bleeding, cerebrovascular disease and postoperative weaning failure in the dead patients from aortic dissection. And also we found that there are some kinds of cause of death not directly related with aortic dissection(sepsis, gastrointestinal bleeding and cerebrovascular disease) in patients, especially in type III. CONCLUSION: Overall four-year survival rate in patients with aortic dissection was 48% and there were no significant differences in survival rate accoring to type, sex and presence of undertaking operation. There were many kinds of cause of death in patients with aortic dissection and some causes of death was not directly related with aortic dissection. The survival rate in patients with aortic dissection will be increased by strict control of blood pressure and optimal timing of operation before development of aortic rupture.
Aortic Rupture
;
Aortic Valve
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Bicuspid
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Blood Pressure
;
Causality
;
Cause of Death
;
Diagnosis
;
Follow-Up Studies*
;
Heart Failure
;
Hemorrhage
;
Humans
;
Hypertension
;
Korea
;
Male
;
Marfan Syndrome
;
Medical Records
;
Mortality
;
Mortuary Practice
;
Renal Insufficiency
;
Retrospective Studies
;
Sepsis
;
Survival Rate
;
Vascular System Injuries
;
Weaning
3.Reference values of differences between TW3-C RUS and TW3-C Carpal bone ages of children from five cities of China.
Shao-yan ZHANG ; Li-juan LIU ; Yi-san HAN ; Gang LIU ; Zhen-guo MA ; Xun-zhang SHEN ; Rui-long XU ; Ji-qing HUA
Chinese Journal of Pediatrics 2008;46(11):851-855
OBJECTIVEThe determination of skeletal maturity has an important role in pediatric clinical practice, especially in relation to endocrinological problems and growth disorders, and it is frequently useful in diagnosis and monitoring treatment. It has been suggested that the difference between radius, ulna and short bonse (RUS) and carpal may be of differential diagnostic significance. However, no data on comparison among bone ages of Chinese children are available. The differences between TW3-Chinese RUS (TW3-C RUS) and TW3-Chinese Carpal (TW3-C Carpal) bone age of Chinese children were observed in this study to provide references for skeletal development estimation.
METHODSTotally 9408 Han healthy children (5066 boys, 4302 girls) aged 1.5 - 13.5 years from 5 cities of China were enrolled in this study. The bone ages of the children were estimated by TW3-C RUS and TW3-C Carpal. The Z score curves of the differences between them were fitted by BCPE distribution and the goodness-of-fit of Box-Cox power exponential distribution (BCPE) models were assessed by Q-test and percents of cases of sample below the fitted percentile curves.
RESULTSThe means of the differences between TW3-C RUS and TW3-C Carpal were -0.19 - 0.17 over the age 2.0 - 13.5 years in boys and -0.12 - 0.13 from age 1.5 - 11.5 years in girls. The standard deviations were respectively 0.47 - 1.01 years for boys and 0.49 - 0.82 years for girls. The degrees of freedom, with respect to the parameter curves from BCPE distribution, were selected and the percentile curves were fitted by BCPE. The differences between percents of cases below the fitted percentile curves and expected values were all under 0.66%, exception of difference for 90th percentile in girls.
CONCLUSIONSThe differences between TW3-C RUS and TW3-C Carpal varied with age, the standard deviations increased gradually before 4.5 years of age in boys and 4 years of age in girls, and afterwards the variations decreased steadily until the TW3-C Carpal has reached full maturity. However, there was sex diversity in the extent of the variations. The differences between TW3-C RUS and TW3-C Carpal for boys were evidently greater than that for girls. The sex difference decreased progressively after 10 years. The proposed Z scores curves charts should provide reference for clinical practice.
Adolescent ; Age Determination by Skeleton ; statistics & numerical data ; Asian Continental Ancestry Group ; Bone Development ; Carpal Bones ; anatomy & histology ; Child ; Child, Preschool ; China ; Female ; Humans ; Infant ; Male ; Radius ; Reference Values ; Ulna ; Urban Population
4.MRI outstands mammogram in sensitivity of breast ductal carcinoma in situ:an analysis of 122 cases.
Qi-xiang YU ; Xiao-song CHEN ; Jia-yi WU ; Bao-san HAN ; Jian-rong HE ; Li ZHU ; Wei-guo CHEN ; Ya-fen LI ; Ling TAN ; Wei-min CHAI ; Deng-bin WANG ; Xiao-chun FEI ; Fei YUAN ; Xiao-long JIN ; Kun-wei SHEN ; Hong-wei LI
Chinese Journal of Surgery 2013;51(1):26-29
OBJECTIVESTo compare the sensitivity of mammogram and breast dedicated MRI in detecting ductal carcinoma in situ with microinvaion (DCIS-MI) and ductal carcinoma in situ (DCIS) lesions, and to further investigate the independent predictive factors of mammogram and MRI sensitivity.
METHODSFrom August 2009 to November 2011, 122 consecutive confirmed breast cancer patients who had received operations were recruited for this clinical research. These patients were divided into two groups including DCIS (72 cases) and DCIS-MI (50 cases) based on pathologic reports. All the patients were female, with mean ages of 52.6 years and 54.4 years. Preoperative bilateral breast mammogram, breast dedicated MRI depictions and reports as well as histopathological reports were collected.
RESULTSSensitivity of MRI outstood mammogram in each subgroups: 84.7% vs. 42.4% in DCIS (χ(2) = 27.028, P = 0.000), 94.0% vs. 80.0% in DCIS-MI group (χ(2) = 4.540, P = 0.040). And further analysis showed that MRI was more sensitive to high nuclear grade DCIS and DCIS-MI lesions than low nuclear grade ones (OR = 3.471, P = 0.031).
RESULTSof logistic regression analysis proved microcalcification was an independent predictive factor of mammogram sensitivity (OR = 11.287, P = 0.001).
CONCLUSIONSSensitivity of breast dedicated MRI is superior to mammogram in detecting DCIS and DCIS-MI groups. Lesions with microcalcifiation is an independent predictive marker which meant that mammogram would achieve high detection rate in cancers presented calcification on mammogram image when compared with non-calcification. Diagnostic performance of breast MRI is less affected by clinical and pathological characteristics of the early stage breast cancer patients but further increased detection rate is observed in DCIS and DCIS-MI with high nuclear grade lesions which indicated that MRI could detect more early stage cancers with relative more aggression biological behaviour and provide these patients with early surgical interventions before possible progression to invasive breast cancers.
Breast Neoplasms ; diagnosis ; Calcinosis ; diagnosis ; Carcinoma, Ductal, Breast ; diagnosis ; Carcinoma, Intraductal, Noninfiltrating ; diagnosis ; Female ; Humans ; Magnetic Resonance Imaging ; Mammography ; Middle Aged ; Sensitivity and Specificity
5.Prognosis of unprotected left main coronary artery stenting and the factors affecting the outcomes in Chinese.
Run-lin GAO ; Bo XU ; Ji-lin CHEN ; Ya-ling HAN ; Zhan-quan LI ; Shu-zheng LÜ ; Xiao-yong QI ; Yong HUO ; Le-feng WANG ; Jun-zhu CHEN ; Wei-feng SHEN ; Wei-yi FANG ; San-qing JIA ; null
Chinese Medical Journal 2006;119(1):14-20
BACKGROUNDThe long term prognosis of unprotected left main coronary artery (LMCA) stenting is controversial. This study was conducted to evaluate the immediate and long term outcomes of LMCA stenting in Chinese patients and to determine which factors affect the outcomes.
METHODSFrom May 1997 to March 2003, 224 patients in 23 hospitals underwent elective unprotected LMCA stenting with bare metal stents. Their clinical records were analysed to ascertain immediate and long term outcomes of LMCA stenting as well as factors influencing the prognosis.
RESULTSStents were implanted into LMCA successfully in 223 cases (99.6 %). One death (0.5%) and one case of non-Q wave nonfatal myocardial infarction (MI) occurred in hospital. The mean follow-up time was (15.6 +/- 12.3) months. Cardiac death developed in 10 cases (4.5%), noncardiac death in 2 cases (0.9%), nonfatal MI in 4 cases (1.8%), target lesion revascularization (TLR) of LMCA in 26 cases (11.7%) and TLR of nonLMCA in 37 cases (16.5%). Univariate analysis showed that cardiac death correlated with left ventricular ejection fraction (LVEF < 40%), female gender and LMCA combined with multivessel disease; that major adverse cardiac events (MACE) correlated with LVEF < 40%, bifurcation lesion and incomplete revascularization. Logistic regression analysis revealed that LVEF < 40% and female gender were independent predictors of cardiac death and MACE. Follow-up angiography was performed in 102 cases (45.7%). The restenosis rate was 31.4%.
CONCLUSIONSLong-term outcomes of stenting for selected patients with unprotected LMCA stenosis is acceptable. It should be performed in inoperable or low risk patients with LVEF > or = 40% and isolated LMCA disease or LMCA combined with multivessel diseases in whom complete revascularization can be obtained.
Adult ; Aged ; Aged, 80 and over ; Coronary Angiography ; Coronary Disease ; therapy ; Coronary Restenosis ; etiology ; Female ; Humans ; Male ; Middle Aged ; Prognosis ; Retrospective Studies ; Stents ; adverse effects ; Treatment Outcome
6. Effect of draxin knockdown on the projection of 23C10-positive neural fibers in the embryonic chick hindbrain
Zi-Yi WANG ; Shu-Han ZHANG ; Zi-Ren ZHANG ; Wen-Wen ZHANG ; Ya-Nan HU ; Yu-Hong SU ; San-Bing ZHANG
Acta Anatomica Sinica 2022;53(4):418-423
[Abstract] Objective To investigate the effects of the downregulation of draxin expression on the projection characteristics of 23C10-positive neural fibers in the chick embryonic hindbrain. Methods The vitro incubation of HH stages 21-22 chick embryonic hindbrain biopsy with alkaline phosphatase (ALP) protein was used as control group. The incubation of HH stages 21-22 chick embryonic hindbrain biopsy with draxin-ALP fusion protein was used as experimental group. The number of embryonic hindbrain for each group was 10. To detect whether 23C10-positive neural fibers could directly bind to draxin protein or not;In ovo electroporation using empty vector in the chick embryonic hindbrain was used as control group. In ovo electroporation with small interfering RNA(siRNA) expressing vector for reducing draxin expression in the chick embryonic hindbrain was used as experimental group. The number of embryonic hindbrain for each group was 18. The effect of the down-regulation of draxin expression and the change of projection characteristics of 23C10-positive neural fibers were observed to check whether the down-regulation of draxin expression would affect the distribution of 23C10-positive fibers. Results Most portion of draxin protein could overlap with 23C10-positive neural fibers in HH stages 21-22 chick embryonic hindbrain biopsies; After expression of the siRNA plasmid against draxin by electroporation, the expression level of draxin protein was significantly reduced, and the distribution of 23C10-positive fibers was scattered in the dorsal hindbrain on the electroporated side at HH stages 25-26 of chick embryos (P < 0. 05) . Conclusion Draxin protein may directly bind to 23C10-positive fibers in hindbrain, and it plays an important regulatory role in the fasciculation of 23C10-positive fibers during chick embryonic development.
7.Effects of saikosaponin b_2 on inflammation and energy metabolism in mice with acute liver injury induced by LPS/GalN.
Man YOU ; Rui-Fang LI ; Zi-Han GAO ; Yuan-Ye LI ; Wei-Yi LIU ; Jian-Gang WANG ; Hong-Wei WANG ; San-Qiang LI
China Journal of Chinese Materia Medica 2019;44(14):2966-2971
To study the effects of saikosaponin b2( SS-b2) on inflammatory factors and energy metabolism against lipopolysaccharide/galactosamine( LPS/Gal N) induced acute liver injury in mice. Mice were randomly divided into normal group( equal amount of normal saline),model group( 100 g·kg~(-1) LPS and 400 mg·kg~(-1) Gal N),low,medium,high dose group of SS-b2( SS-b25,10,20 mg·kg~(-1)·d-1) and positive control group( dexamethasone,10 mg·kg~(-1)). All of the groups except for the normal group were treated with LPS/Gal N though intraperitoneally injection to establish the acute liver injury model. The organ indexes were calculated. The levels of serum transaminases( ALT and AST) and the activities of ATPase( Na+-K+-ATPase,Ca2+-Mg2+-ATPase) in liver were detected. The activity of tumor necrosis factor-α( TNF-α),interleukin-1β( IL-1β) and interleukin-6( IL-6) were determined by the enzyme-linked immunosorbent assay( ELISA). The contents of lactate dehydrogenase( LDH) in liver were determined by micro-enzyme method. HE staining was used to observe the histopathological changes of the liver. Histochemical method was used to investigate the protein expression of liver lactate dehydrogenase-A( LDH-A). The protein expressions of Sirt-6 and NF-κB in the liver were detected by Western blot. According to the results,compared with the model group,there were significant changes in organ indexes in the high-dose group of SS-b2( P<0. 05). The level of ALT,AST,TNF-α,IL-1β,IL-6 and the activities of LDH in serum of mice with liver injury were significantly reduced in the medium and high dose groups of SS-b2( P<0. 01). With the increase of the concentration of SS-b2,the range of hepatic lesions and the damage in mice decreased. The activities of Na+-K+-ATPase and Ca2+-Mg2+-ATPase in liver of mice were significantly enhanced in each dose group( P<0. 01). The expression of NF-κB in liver tissues was significantly down-regulated in the medium and high dose group( P<0. 01). Meanwhile,the expression of Sirt-6 protein in the liver of mice with acute liver injury was significantly increased in each dose group( P<0. 01).In summary,SS-b2 has a significant protective effect on LPS/Gal N-induced acute liver injury in mice,which may be related to the down-regulation of NF-κB protein expression and up-regulation of Sirt-6 protein expression to improve inflammatory injury and energy metabolism.
Animals
;
Chemical and Drug Induced Liver Injury
;
drug therapy
;
Cytokines
;
metabolism
;
Energy Metabolism
;
Galactosamine
;
Inflammation
;
drug therapy
;
Lipopolysaccharides
;
Liver
;
drug effects
;
Mice
;
NF-kappa B
;
metabolism
;
Oleanolic Acid
;
analogs & derivatives
;
pharmacology
;
Random Allocation
;
Saponins
;
pharmacology
;
Sirtuins
;
metabolism
8.Research progress of Phyllanthi Fructus and prediction of its Q-markers.
Hao-Zhou HUANG ; Jing-Cai CHEN ; Ding-Kun ZHANG ; Meng-Qi LI ; Qin-Chi XIAN ; San-Hu FAN ; Peng TAN ; Wan-Min MAO ; Feng LIN ; Jun-Zhi LIN ; Li HAN
China Journal of Chinese Materia Medica 2021;46(21):5533-5544
Phyllanthi Fructus, a unique Chinese and Tibetan medicinal plant with both edible and medical values, has high potential of cultivation and development. The resources of Phyllanthi Fructus in China are rich, mainly distributed in Yunnan, Sichuan, Fujian, Guangdong, Guangxi, etc. Phyllanthi Fructus is widely used in the clinical practice of Chinese medicine and plays an important role in Tibetan medicine, Uyghur medicine, Yi medicine, and Mongolian medicine. Phyllanthi Fructus mainly contains phenolic acids,tannins, terpenes, sterols, fatty acids, flavonoids, amino acids and other compounds. Modern pharmacological studies show that Phyllanthi Fructus has antioxidant, anticancer, blood lipid-lowering, liver protective, antimicrobial, anti-inflammatory, and immune regulatory activities. In this paper, the research status of Phyllanthi Fructus was reviewed from the aspects of herbal textual research,chemical composition, and pharmacological action. The quality markers(Q-markers) of Phyllanthi Fructus were predicted and analyzed from the aspects of biogenic pathway, specificity and measurability of chemical components, efficacy, properties, new clinical uses, drug-food homology, and transformation of polyphenols. The results will provide a scientific basis for the quality control, quality evaluation, and standard formulation of Phyllanthi Fructus.
China
;
Drugs, Chinese Herbal
;
Fruit
;
Medicine, Tibetan Traditional
;
Quality Control
9.Adult dental epithelial stem cell-derived organoids deposit hydroxylapatite biomineral.
Hyun-Yi KIM ; Victoria COOLEY ; Eun-Jung KIM ; Shujin LI ; Jong-Min LEE ; Dina SHEYFER ; Wenjun LIU ; Ophir D KLEIN ; Derk JOESTER ; Han-Sung JUNG
International Journal of Oral Science 2023;15(1):55-55
Ameloblasts are specialized cells derived from the dental epithelium that produce enamel, a hierarchically structured tissue comprised of highly elongated hydroxylapatite (OHAp) crystallites. The unique function of the epithelial cells synthesizing crystallites and assembling them in a mechanically robust structure is not fully elucidated yet, partly due to limitations with in vitro experimental models. Herein, we demonstrate the ability to generate mineralizing dental epithelial organoids (DEOs) from adult dental epithelial stem cells (aDESCs) isolated from mouse incisor tissues. DEOs expressed ameloblast markers, could be maintained for more than five months (11 passages) in vitro in media containing modulators of Wnt, Egf, Bmp, Fgf and Notch signaling pathways, and were amenable to cryostorage. When transplanted underneath murine kidney capsules, organoids produced OHAp crystallites similar in composition, size, and shape to mineralized dental tissues, including some enamel-like elongated crystals. DEOs are thus a powerful in vitro model to study mineralization process by dental epithelium, which can pave the way to understanding amelogenesis and developing regenerative therapy of enamel.
Mice
;
Animals
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Durapatite/metabolism*
;
Dental Enamel/metabolism*
;
Ameloblasts/metabolism*
;
Amelogenesis
;
Stem Cells
;
Organoids